Mini review: linkage between α-Synuclein protein and cognition

Translational Neurodegeneration

Rena Li⁴  Yong Shen³  Jie Cui²  Hailan Yao¹  Ayeh Saleh¹  Huda Saleh¹ 

[1] Center for Advanced Therapeutic Strategies for Brain Disorders Roskamp Institute, Sarasota 34243, FL, USA;Center for Hormone Advanced Science and Education, Roskamp Institute, Sarasota 34243, FL, USA;Neurodegenerative Disease Research Center, School of Life Sciences, University of Science and Technology of China, Anhui 230027, China;Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100088, China

关键词: Alzheimer’s disease;    Learning;    Memory;    Cognition;    Parkinson’s disease;    α-Synuclein;   

Others  :  1172214
DOI  :  10.1186/s40035-015-0026-0

 received in 2015-02-09, accepted in 2015-03-17,  发布年份 2015

【 摘 要 】

α-synuclein is a protein that plays important roles in cognitive function in the normal brain, although its exact role is not fully understood. However, current studies reveal that defects in α-synuclein function could contribute to various neurodegenerative disorders, such as Parkinson’s disease (PD), a disease with symptomatic progression of deterioration in motor and cognitive function. Recent studies show that the level of α -synuclein in cerebrospinal fluid (CSF) is highly correlated with speed of cognitive decline, suggesting a potential role of α-synuclein in cognitive function. In this mini review, we will be focus on literatures of α-synuclein in cognitive function in the non-diseased brain, as well as the impact that defective α-synuclein has on cognition in disease brain. This will be accomplished by assessing the effects of soluble α-synuclein, α-synuclein oligomers, and extracellular α-synuclein transport, on neurodegeneration.

【 授权许可】

   
2015 Saleh et al.; licensee BioMed Central.

【 参考文献 】

• [1]Kim H: Alphα -synuclein expression in patients with Parkinson’s disease: a clinician’s perspective. Exp Neurobiol 2013, 22(2):77-83.
• [2]Mossuto MF: Disulfide bonding in neurodegenerative misfolding diseases. Int J Cell Biol 2013, 2013:318319.
• [3]Mehta AK, Rosen RF, Childers WS, Gehman JD, Walker LC, Lynn DG: Context dependence of protein misfolding and structural strains in neurodegenerative diseases. Biopolymers 2013, 100(6):722-30.
• [4]Kang JH, Irwin DJ, Chen-Plotkin AS, Siderowf A, Caspell C, Coffey CS, et al.: Association of cerebrospinal fluid β-amyloid 1-42, T-tau, P-tau181, and α-synuclein levels with clinical features of drug-naive patients with Parkinson disease. JAMA Neurology 2013, 70(10):1277-87.
• [5]Wilkaniec A, Strosznajder JB, Adamczyk A: Toxicity of extracellular secreted alpha synuclein: its role in nitrosative stress and neurodegeneration. Neurochem Int 2013, 62(5):776-83.
• [6]Nagano-Saito A, Habak C, Mejia-Constain B, Degroot C, Monetta L, Jubault T, et al.: Effect of mild cognitive impairment on the patterns of neural activity in early Parkinson’s disease. Neurobiol Aging 2014, 35(1):223-31.
• [7]Pereira JB, Junque C, Bartres-Faz D, Ramirez-Ruiz B, Marti MJ, Tolosa E: Regional vulnerability of Hippocampal subfields and memory deficits in Parkinson’s disease. Hippocampus 2013, 23(8):720-8.
• [8]Korff A, Liu C, Ginghina C, Shi M, Zhang J: α-synuclein in cerebrospinal fluid of Alzheimer’s disease and mild cognitive impairment. J Alzheimer Dis 2013, 36(4):679-88.
• [9]Kalia LV, Kalia SK, McLean PJ, Lozano AM, Lang AE: Alpha‐synuclein oligomers and clinical implications for Parkinson disease. Ann Neurol 2013, 73(2):155-69.
• [10]Bartels T, Choi JG, Selkoe DJ: Alpha-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation. Nature 2011, 477(7362):107-10.
• [11]Bonini NM, Giasson BI: Snaring the function of α-synuclein. Cell 2005, 123(3):359-61.
• [12]Abeliovich A, Schmitz Y, Fariñas I, Choi-Lundberg D, Ho WH, Castillo PE, et al.: Mice lacking α-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron 2000, 25(1):239-52.
• [13]Manning-Bog AB, McCormack AL, Purisai MG, Bolin LM, Di Monte DA: α-synuclein overexpression protects against paraquat-induced neurodegeneration. J Neurosci 2003, 23(8):3095-9.
• [14]Darios F, Ruipérez V, López I, Villanueva J, Gutierrez LM, Davletov B: Alpha‐Synuclein sequesters arachidonic acid to modulate SNARE‐mediated exocytosis. EMBO Rep 2010, 11(7):528-33.
• [15]Kokhan VS, Afanasyeva MA, Van’kin GI: α-synuclein knockout mice have cognitive impairments. BehavBrain Res 2012, 231(1):226-30.
• [16]Chen PE, Specht CG, Morris R, Schoepfer R: Spatial learning is unimpaired in mice containing a deletion of the alphα -synuclein locus. Eur J Neurosci 2002, 16(1):154-8.
• [17]Ullman O1, Fisher CK, Stultz CM: Explaining the structural plasticity of α-synuclein. J Am Chem Soc 2011, 133(48):19536-46.
• [18]Illes-Toth E, Dalton CF, Smith DP: Binding of dopamine to alphα -synuclein is mediated by specific conformational states. J Am Soc Mass Spectrom 2013, 24(9):1346-54.
• [19]Colloby SJ, McParland S, O’Brien JT, Attems J: Neuropathological correlates of dopaminergic imaging in Alzheimer’s disease and Lewy body dementias. Brain: AJournal of Neurology 2012, 135(9):2798-808.
• [20]Fantini J, Yahi N: The driving force of alphα -synuclein insertion and amyloid channel formation in the plasma membrane of neural cells: Key role of ganglioside-and cholesterol-binding domains. Adv Exp Med Biol 2013, 991:15-26.
• [21]Diogenes MJ, Dias RB, Rombo DM, Vicente Miranda H, Maiolino F, Guerreiro P, et al.: Extracellular alphα -synuclein oligomers modulate synaptic transmittion and impair LTP via NMDA-receptor activation. J Neurosci 2012, 32(34):11750-62.
• [22]Resende R, Marques SC, Ferreiro E, Simoes I, Oliveira CR, Pereira CM: Effect of α-synuclein on amyloid β-induced toxicity: relevance to Lewy body variant of Alzheimer disease. Neurochem Res 2013, 38(4):797-806.
• [23]Stefanis L: α-synuclein in Parkinson’s disease. Cold Spring Harbor Perspectives in Medicine 2012, 2(2):a009399.
• [24]Tateno F, Sakakibara R, Kawai T, Kishi M, Murano T: Alpha-synuclein in the cerebrospinal fluid differentiates synucleinopathies (Parkinson Disease, dementia with Lewy bodies, multiple system atrophy) from Alzheimer disease. Alzheimer Dis Assoc Disord 2012, 26(3):213-6.
• [25]Vasudevaraju P, Guerrero E, Hegde ML, Collen TB, Britton GB, Rao KS: New evidence on alpha-synuclein and Tau binding to conformation and sequence specific GC* rich DNA: Relevance to neurological disorders. J Pharm Bioallied Sci 2012, 4(2):112-7.
• [26]Marques O, Outeiro TF: Alphα -synuclein:from secretion to dysfunction and death. Cell Death and Disease 2012, 3:e350.
• [27]Guo JL, Covell DJ, Daniels JP, Iba M, Stieber A, Zhang B, et al.: Distinct alpha-synuclein strains differentially promote tau inclusions in neurons. Cell 2013, 154(1):103-17.
• [28]Wang DS, Bennett DA, Mufson E, Cochran E, Dickson DW: Decreases in soluble alpha-synuclein in frontal cortex correlate with cognitive decline in the elderly. Neurosci Lett 2004, 359(1–2):104-8.
• [29]Rao AV, Balachandran B: Role of oxidative stress and antioxidants in neurodegenerative diseases. Nutr Neurosci 2002, 5(5):291-309.
• [30]Martin ZS, Neugebauer V, Dineley KT, Kayed R, Zhang W, Reese LC, et al.: alpha-Synuclein oligomers oppose long-term potentiation and impair memory through a calcineurin-dependent mechanism: relevance to human synucleopathic diseases. J Neurochem 2012, 120(3):440-52.
• [31]Grathwohl SA, Steiner JA, Britschgi M, Brundin P: Mind the gut: secretion of alpha-synuclein by enteric neurons. J Neurochem 2013, 125(4):487-90.
• [32]Chai YJ, Kim D, Park J, Zhao H, Lee SJ, Chang S: The secreted oligomeric form of alpha-synuclein affects multiple steps of membrane trafficking. FEBS Lett 2013, 587(5):452-9.
• [33]Larson ME, Sherman MA, Greimel S, Kuskowski M, Schneider JA, Bennett DA, et al.: Soluble alpha-synuclein is a novel modulator of Alzheimer’s disease pathophysiology. J Neurosci 2012, 32(30):10253-66.
• [34]Xu G, Stevens SM Jr, Moore BD, McClung S, Borchelt DR: Cytosolic proteins lose solubility as amyloid deposits in a transgenic mouse model of Alzheimer-type amyloidosis. Hum Mol Genet 2013, 22(14):2765-74.
• [35]Hamilton RL: Lewy bodies in Alzheimer’s disease: a neuropathological review of 145 cases using alpha-synuclein immunohistochemistry. Brain Pathol 2000, 10(3):378-84.
• [36]Jellinger KA, Attems J: Prevalence and impact of vascular and Alzheimer pathologies in Lewy body disease. Acta Neuropathol 2008, 115(4):427-36.
• [37]Postuma RB: Comment: epidemiology of dementia with Lewy bodies–the Alzheimer-Parkinson overlap. Neurology 2013, 81(9):838.
• [38]Li J, Liu D, Sun L, Lu Y, Zhang Z: Advanced glycation end products and neurodegenerative diseases: mechanisms and perspective. J Neurol Sci 2012, 317(1–2):1-5.
• [39]Gold A, Turkalp ZT, Munoz DG: Enteric alpha-synuclein expression is increased in Parkinson’s disease but not Alzheimer’s disease. Mov Disord 2013, 28(2):237-40.
• [40]Irwin DJ, Abrams JY, Schonberger LB, Leschek EW, Mills JL, Lee VM, et al.: Evaluation of potential infectivity of Alzheimer and Parkinson disease proteins in recipients of cadaver-derived human growth hormone. JAMA Neurol 2013, 70(4):462-8.
• [41]Hashimoto M, Rockenstein E, Mante M, Crews L, Bar-On P, Gage FH, et al.: An antiaggregation gene therapy strategy for Lewy body disease utilizing beta-synuclein lentivirus in a transgenic model. Gene Ther 2004, 11(23):1713-23.
• [42]Ghanbari HA, Potomac MD, Ghanbari K: Compositions and methods for preventing protein aggregation in neurodegenerative diseases. United States Patient Application Publication, United States; 2012.
• [43]Weinreb O: Neurological mechanisms of polyphenols in Alzheimer’s and Parkinson’s diseases. J Nutr Biochem 2004, 15(9):506-16.